Colony stimulating factors (hereinafter referred to as "CSFs") are endogenous factors promoting the proliferation and differentiation of granulocytes and macrophages. The CSFs act on stem cells of the bone marrow granulocytic and macrophage series (GM-CFUs) and are classified, for example, into 1) G-CSF (granulocyte CSF) causing formation of granulocytes, 2) M-CSF (macrophage CSF) causing formation of monocytic macrophages, and 3) GM-CSF causing formation of both granulocytes and macrophages. CSF which belongs to M-CSF and does not act directly on the GM-CFUs but acts on monocytes in the blood to thereby promote secretion of GM-CSF and indirectly cause proliferation of macrophages and granulocytes, has also been purified from human urine (hereinafter referred to as "CSF-HU").
The immunoactivating agent has been used as a means of cancer immunotherapy and, specific examples thereof include Picibanil (OK-432), Krestin (PSK), lentinan and schizophyllan. Picibanil is a polysaccharide in the form of dry powder prepared by lyophilizing the strain of Streptococcus piogenes A-III-Su previously treated with penicillin (manufactured by Chugai). Krestin is hot water extract of mycelium of Criolus versicolor, which containing mainly a-protein-binding polysaccharide (manufactured by Kureha-Sankyo). Lentinan is a .beta.-1,3-glucan extracted from fruit body of Leutinus ebodes (manufactured by Ajinomoto-Morishita-Yamanouchi). Schizophyllan is a polysaccharide, containing .beta.-1,3-glucan as a main chain and .beta.-1,6-glucan as a side chain, derived from culture medium of Schizophyllum commune (GANN, 60, 137-144 (1969)).
The mechanisms of action of such immunoactivating agent are considered such that it acts on lymphocytes to cause secretion of an endogenous TNF (tumor necrosis factor) or a TNF-like substance and thereby increase the in vivo TNF activity and, as a result, an antitumor effect is produced.
Although such immunoactivating agents do not produce severe adverse effects and are useful antitumor agents, their activity is not so potent and satisfactory effects are not always obtained.